Many new psychoactive substances (NPS) under different names throughout the world, Macedonia and Slovenia included, have emerged in the past few years. The most common names are: designer drugs, legal highs, herbal highs, research chemicals, bath salts, plant food etc. The substances are usually marked as not for human consumption. They are synthetic or plant based mostly sold on the internet or shops known as smart shops or head shops. These substances are not protected with the international legislation. Users’ experience can be tracked on social networks or forums. NPS’s users are also known as “psychonauts.”
According the European Monitoring Centre for Drugs and Drugs Addiction (EMCDDA), a total of 164 new psychoactive substances were officially notified from 2005 to 2011 via the EU Early Warning System. In 2011, for the third time in a row, the largest number of new substances – 49 – was reported in Europe, which is more than the 41 in 2010 and the 24 substances in 2009. Around 2/3 of the newly notified substances in 2011 were synthetic cannabinoids or synthetic cathinones. In 2012, 73 new psychoactive substances were officially notified. The dominant substances in the last few years are mostly synthetic cannabinoid agonists (CRA), phenethylamine and cathinones, which imitate the effects of the most desired illicit drugs. In addition, the number of internet stores in EU that provide clients with psychoactive substances or products has also increased. In January 2012, 693 internet stores were discovered, which is more than the 314 in January and 170 in January 2011. Apart from the aforementioned sources, NPS can also be purchased with the mediation of street sellers.
The growing trend in new drugs can easily be tracked in the daily clinical practice of those working with people dependent on illicit drugs.
What are the new psychoactive substances?
NPS are substances of abuse (either in pure form or a preparation) not controlled by the existing conventions (the Single Convention on Narcotic Drugs from 1961 or the Convention on Psychotropic Substances from 1971), but may pose a public health treat. These substances are legal alternative to controlled substances, i.e. drugs. The name itself, new psychoactive substances, doesn’t refer only to innovative drugs, but also to substances that have been more available recently. One of the first NPS is ketamine, followed by phenethylamine, piperazines, synthetic cannabinoids, synthetic cathinones and others.
Madras divides the so-called designer drugs into four major groups: synthetic cathinones and amphetamines (mephedrone, MDPV, methylone etc.), synthetic cannabinoids (JWH-018, 073 – JWH is an abbreviation of John W. Huffman’s name, the person who synthesised the substance, AM-694 8, Hu-201, CP-47 etc.), hallucinogens (Br-Fly) and synthetic opioids (desomorphine – the so-called crocodile).
Mostly, these substances are not with natural origin (as are usually marketed), but are synthesized in laboratories in Europe and Asia (mostly China and India). For the time being, the standard urine tests used daily in the clinical practice cannot detect them. The market has already offered tests which detect some of the substances from the synthetic cannabinoids group. The fact that a certain substance is still legal can offer false sense of safety, i.e. lack of harmful effects. The offer quickly adjusts to the market. Once the substance in question is listed as prohibited the laboratories immediately synthesize a new one. It can be quite similar to the first one, however the slightest change in its chemical structure lists it back among the legal substances. There are the so-called anonymous networks, i.e. “darknets”, where NPS can be purchased. The technology required to visit these networks is now included in the standard program equipment, which makes it available for a broader circle of people. All of this, in addition to the convenient price, is the reason why young users reach to the new drugs. According to the information released by DrogArt, a Slovenian NGO, NPS’s use is very popular with MSM (men who have sex with men), which leads to the occurrence of the so-called “chem-sex”, mostly because of the risky sexual behaviour associated with NPS use (the risk of sexually transmitted diseases). The fact that these substances are not researched shouldn’t be disregarded. There is no data on the pharmacodynamics and pharmacokinetics or the possible long-term consequences on the mental or physical health. The short-term negative (toxic) effects are known only from clinical cases. The use if NPS has also led to a number of death cases.
SIDE EFFECTS OF NEW PSYCHOACTIVE SUBSTANCES
Research in the field of NPS is exceptionally rare. There are certain descriptions of clinical cases available (mostly intoxication). The long-term effects regarding the use of these substances are almost unknown. The listed adverse effects are from mild to life threatening effects on the cardiovascular, nervous, gastrointestinal and respiratory system. There is a wide spectre of possible psychiatric complications with the use of these drugs and complications in users who suffer from mental diseases. Theory mostly lists: agitation, insomnia, difficulty concentrating, transitory paranoia, distorted perception, anxiety, transitory changes in the mood, delirium or even serious psychotic conditions, as well as suicidal impulses.
Further below we list the most common psychological side effects of the mostly used NPS.
SYNTHETIC CANNABINOID RECEPTOR AGONISTS (CRA) – SYNTHETIC CANNABINOID AND CATHINONES AND THEIR SIDE EFFECTS
Synthetic cannabinoid receptor agonists (CRA) – synthetic cannabinoids (also found as “spice,“ “K2,“ “spice gold“, “spice silver“, “bliss“, “black mamba,“ “JWH-018,-073,-250,“ “mr. smiley“ etc) are a type of legal alternative to marihuana. The effects are similar to those of marihuana – relaxation, sedation, euphoria and altered perception. Contrary to tetrahydrocannabinol (THC), found in marihuana and categorized as partial agonist of cannabinoid CB1 receptors, their effects are often related not only to CB1 but cannabinoid CB2 receptors also, as full agonists. Partial agonists reach the so-called “plateau effect” (in terms of dosage/clinical effects), full agonists do not reach the so-called “plateau effect,” hence use of synthetic cannabinoids leads to a greater risk of overdose and severe toxic consequences with longer effects than marihuana use.
Synthetic cannabinoids do not contain cannabidiol (CBD) which, among others, has antipsychotic affects. CBD is found in marihuana, hence is assigned with a protective role. The listed side effects are: agitation, distortion in time perception, anxiety, dysphoria, hallucinations and paranoia. There have been cases of induced psychotic symptoms in people who used cannabinoids and deterioration in these psychotic symptoms in people with psychosis. The listed peripheral side effects are: gastrointestinal distress (sickness, vomiting), cardiovascular complications (increased blood pressure, rapid heart rate, cardiac ischemia), metabolic effects (hypocalemia, hyperglycemia, acidosis), effects on the nervous system (dilated pupils, increased body temperature, nystagmus, convulsions, coma), acute renal failure.
The second important group of new psychoactive substances is the synthetic cathinones. They are synthetic analogues of naturally occurring compounds found in the plant Catha edulis. They are a class of stimulants of the central nervous system (CNS), also psycho-stimulants and can be hallucinogenic in higher dosage. They exert their effects by inhibiting the reuptake of monoamines – serotonin, dopamine and noroadrenaline and have strong sympathomimetic effects. They can cause euphoria, alertness, increased energy, a need to be active, decrease the appetite, improve the sense of music, influence the sexual activity, i.e. behaviour (increased libido and increased pleasure during sexual intercourse), as well as empathogenic effects (mostly in mephedrone). The listed substances are MDPV (3,4- methylenedioxypyrovalerone), mephedrone („m-cat“, „meph“, „miaow“), methylone („bk-MDMA“, „explosion“, „top cat“), 4-BMC, NEB, MOPPP, MDPPP, 3-MMC (found as ice cream) and many others.
The described side effects are cardiovascular, neurological, respiratory, gastrointestinal and psychiatric. For instance, agitation, psychosis, (hallucinations, paranoia, delusions), suicidal urges, aggression, anxiety, insomnia; sometimes the symptoms resemble to those of delirium (disorganization, disorientation, attention deficit disorder and memory loss).
Listed side effects are also: hypertension, rapid heart rate, QT prolongation, pain in the chest, convulsions, brain edema, tremor, Parkinson’s disease, headaches, paresthesias, nose bleeds, difficulty in breathing, weakness, vomiting, stomachaches, serotonin syndrome, kidney failure, hyponatremia etc.
Other NPS are piperazine (c CPP, BZP etc.), mostly sold as ecstasy, ketamines and phenethylamines (2C-C-NBOMe – street name “nebome,“ “dragonfly“).
The current situation in Macedonia and Slovenia
Macedonia also has the first clients who use NPS from the group of synthetic cannabis. Although in the past few years, people who use marihuana felt that Macedonia has to offer “good marihuana,” and they refused to use synthetic cannabis, nowadays clients report on the use of synthetic cannabis and presence of NPS purchased online. They also report on lack of marihuana (illicit drugs) on the black market lately, as well as an increase in its price, which, other factors aside, can also lead to the use of synthetic cannabis instead. There is still no research on the use of NPS in the country. The existing screening tests for toxicological analysis used in health institutions and laboratories available in the country cannot detect presence of these substances in the urine, while experts are not sufficiently prepared to face the challenges triggered by the use of the new legal psychoactive substances.
According to the information of the NGO DrogArt, the most used new psychoactive substances in Slovenia are: 3-MMC (3-methylmethcathinone), 4-MEC (4- methoxymethcathinone), GHB/GBL (gamma–hydroxybutyric acid, gamma-butyrolactone), methylone (street name „bka“), 4-FA (4-fluoroamphetamine ), 25x-NBOMe (street name „nebome“), AMT (alfa–metiltriptamin), 2-CB (2,5-dimethoxy-4-bromophenethylamine) and other related substances.
Judging by the results from the 2013-2014 research on NPS use in Slovenia by Sande and his collaborators, cathinones are the most common and favourite NPS group used in Slovenia. There is also the tendency to use larger dosages in one – „BINGEY“ (long-term, uncontrolled and repetitive use). The average age of the respondents in the research was 23. Almost one fourth were high school students, leading to the conclusion that NPS users are quite young. The most used among the cathinones in Slovenia is 3-MMC, or ice cream. The reason NPS users list is the pleasant effects, price and availability, rather than it being legitimate.
WHAT IS ICE CREAM?
3-MMC (3-methylmethcathinone) is also referred to as ice cream. It is an isomer of the favourite mephedrone, i.e. 4-MMC, whose use has decreased in the past few years. It is found in the form of crystals, white powder, used orally or nasally. It causes changes in consciousness, pleasure, euphoria, warmth, love, confusion, relaxation. It can cause severe side effects (confusion, shaking, palpitations, arrhythmia, chest pains, stomach pains, convulsions, epileptic seizures, hyperthermia, blue or cold fingers, changes in the mood, i.e. depression). Users describe a strong urge (psychic crisis – „craving”) for the substance that can last up to an hour, which is why it is a potential danger leading to dependence. It is spread among the young population (apart from high school students, students from elementary schools are also suspected of using it).
Gamma–hydroxybutyric acid (GHB, „G“, Liquid Ecstasy, Liquid Scoop, Soap, Salty Water, Cherry Meth etc.) and its precursor GLB, although not in the NPS group, must be mentioned because of their frequent use and possible complications. It can be found in the form of a liquid with no colour or odour, powder and capsules. Users mostly mix it in drinks. Small doses cause relaxation, possibly euphoria, it increases the sexual urge, making the user more communicative and sociable. Larger dosages cause vertigo, confusion, loss of memory and convulsions. It can also lead to addiction. Frequent and long-term use leads to physical dependence. Early abstinence syndromes are similar to those of alcohol dependence (possible symptoms of delirium, psychosis, or catatonia). Abstinence syndromes occur 1 to 6 hours later, as anxiety, tremor, insomnia, sickness, vomiting, paranoia, intense hallucinations, changes in memory and aggression, leading to death if not treated. The abstinence crisis lasts from 3 to 21 days, and it is treated with benzodiazepines, while other countries also use baclofen (GABA-B agonist), barbiturates and propofol. The manner in which it is dosed (drops, spoonfuls), can lead to overdose or even possible death.
Finally, we would like to mention that NPS use (mostly synthetic cathinone) has spread to other European countries even among intravenous drug users (heroin or amphetamine users), who also use NPS intravenously.
The new NPS with its specific market characteristics and the less known, for the time being, side effects on the physical and mental health require in-depth research and study not only to recognize the acute conditions after their use, but rather to adjust the existing treatment and programs for reduction of drug related harms with the current needs on the field. The programs should keep the pace with time, i.e. adjust the patients’ needs and be constantly up-to-date with the trends.
Docent d-r Liljana Ignjatova is the Head of the Centre for Prevention and Treatment of Drug Abuse and Abuse of Other Psychoactive Substances at the PHI Psychiatric Hospital “Skopje,” Macedonia, and a Docent in Psychiatry and Medical Psychology at the Medical Faculty at the St. Cyril and Methodius University in Skopje. Doc. D-r Igjnatova is a founding member of the Board of Directors of the SEE Adriatic Addiction Treatment Network, as well as a founding member of the World Federation for the Treatment of Opiate Dependence. She is a permanent correspondent from Macedonia for Pompidou Group, Council of Europe. In 2015 she was awarded with the SEE net Reflection Award.
Andrej Kastelic is a doctor in medical sciences. He is the head of the National Centre for Treatment of Drug Addiction in Ljubljana (Slovenia) and president of co-ordination of the Centers for Prevention and Treatment of Drug Addiction at the Ministry of Health of the Republic of Slovenia. He is also a consultant for UNAIDS, UNODC, WHO, EU, the Pompidou Group of the Council of Europe, OSCE, the Global Fund to Fight AIDS, Tuberculosis and Malaria, as well as a lecturer and consultant in different countries throughout the world.
Nuša Šegrec is a psychiatrist at the Centre for Treatment of Drug Addiction at the University Psychiatric Hospital Ljubljana, Slovenia. She specializes in working with people who use drugs with complex needs and comorbid mental diseases.
Biljana Stojceska is a specialist in neurology, at present specializing in psychiatry in Ljubljana, Slovenia. She works at the Neuropsychiatry Unit at the General Hospital in Prilep.